Darboe M.K.,MRC International Nutrition Group |
Fulford A.J.C.,MRC International Nutrition Group |
Secka O.,MRC Laboratories |
Prentice A.M.,MRC International Nutrition Group
BMC Infectious Diseases | Year: 2010
Background: Streptococcus pneumoniae is an important cause of community acquired pneumonia, sepsis, meningitis and otitis media globally and has been incriminated as a major cause of serious childhood bacterial infections in The Gambia. Better understanding of the dynamics of transmission and carriage will inform control strategies.Methods: This study was conducted among 196 mother-infant pairs recruited at birth from six villages in the West Kiang region of The Gambia. Nasopharyngeal swabs were collected from mother-infant pairs at birth (within 12 hours of delivery), 2, 5 and 12 months. Standard techniques of culture were used to identify carriage and serotype S. pneumoniae.Results: Of 46 serotypes identified, the 6 most common, 6A, 6B, 14, 15, 19F and 23F, accounted for 67.3% of the isolates from infants. Carriage of any serotype among infants rose from 1.5% at birth to plateau at approximately 80% by 2 m (prevalence at 2 m = 77%; 5 m = 86%; 12 m = 78%). Likewise, maternal carriage almost doubled in the first 2 months post-partum and remained elevated for the next 10 m (prevalence at birth = 13%; 2 m = 24%; 5 m = 22%; 12 m = 21%). Carriage was significantly seasonal in both infants and mothers with a peak in December and lowest transmission in August. The total number of different serotypes we isolated from each infant varied and less than would be expected had the serotypes assorted independently. In contrast, this variability was much as expected among mothers. The half-life of a serotype colony was estimated to be 1.90 m (CI95%: 1.66-2.21) in infants and 0.75 m (CI95%: 0.55-1.19) in mothers. While the odds for a serotype to be isolated from an infant increased by 9-fold if it had also been isolated from the mother, the population attributable fraction (PAF) of pneumococcal carriage in infants due to maternal carriage was only 9.5%. Some marked differences in dynamics were observed between vaccine and non-vaccine serotypes.Conclusions: Colonisation of the nasopharynx in Gambian infants by S. pneumoniae is rapid and highly dynamic. Immunity or inter-serotype competition may play a role in the dynamics. Reducing mother-infant transmission would have a minimal effect on infant carriage. © 2010 Darboe et al; licensee BioMed Central Ltd.
Cheung Y.B.,Singapore Clinical Research Institute |
Cheung Y.B.,National University of Singapore |
Xu Y.,Singapore Clinical Research Institute |
Tan S.H.,National Cancer Center |
And 2 more authors.
Statistics in Medicine | Year: 2010
Randomized trials of interventions against infectious diseases are often analyzed using data on first or only episodes of disease, even when subsequent episodes have been recorded. It is often said that the Andersen-Gill (AG) model gives a biased estimate of intervention effect if there is event dependency over time. We demonstrate that, in the presence of event dependency, an effective intervention may have an indirect effect on disease risk at time tj via its direct effect on disease risk at time ti, i
Ahmed S.,Karolinska Institutet |
Ahmed S.,International Center for Diarrhoeal Disease Research |
Ahsan K.B.,International Center for Diarrhoeal Disease Research |
Kippler M.,Karolinska Institutet |
And 7 more authors.
Toxicological Sciences | Year: 2012
Prenatal arsenic exposure is associated with increased infant morbidity and reduced thymus size, indicating arsenic-related developmental immunotoxicity. We aimed to evaluate effects of prenatal arsenic exposure on thymic function at birth and related mechanisms of action. In a Bangladeshi cohort, arsenic was measured in urine (U-As, gestational week (GW) 8 and 30) and blood (B-As, GW14) in 130 women. Child thymic index was measured by sonography at birth and thymic function by signal-joint T-cell receptor-rearrangement excision circles (sjTRECs) in cord blood mononuclear cells (CBMC). In a subsample (n = 44), sjTRECs content in isolated CD4+ and CD8+ T cells, expression of oxidative-stress defense and apoptosis-related genes in CBMC, arsenic concentrations (urine, placenta, and cord blood), and oxidative stress markers in placenta and cord blood were measured. In multivariable-adjusted regression, ln U-As (GW8) was inversely associated with ln sjTRECs in CBMC (B = -0.25; 95% confidence interval [CI] -0.48 to -0.01). Using multivariable-adjusted spline regression, ln U-As (GW30) and ln B-As (GW14) were inversely associated with ln sjTRECs in CBMC (B = -0.53; 95% CI -0.93 to -0.13 and B = -1.27; 95% CI -1.89 to -0.66, respectively) below spline knots at U-As 150 μg/l and B-As 6 μg/kg. Similar inverse associations were observed in separated CD4+ and CD8+ T cells. Arsenic was positively associated with 8-hydroxy-2'-deoxyguanosine in cord blood (B = 0.097; 95% CI 0.05 to 0.13), which was inversely associated with sjTRECs in CD4+ and CD8+ T cells. In conclusion, prenatal arsenic exposure was associated with reduced thymic function, possibly via induction of oxidative stress and apoptosis, suggesting subsequent immunosuppression in childhood. © The Author 2012. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.
de Jong B.C.,MRC Laboratories |
de Jong B.C.,New York University |
de Jong B.C.,Institute of Tropical Medicine |
Antonio M.,MRC Laboratories |
And 2 more authors.
PLoS Neglected Tropical Diseases | Year: 2010
Mycobacterium africanum consists of two phylogenetically distinct lineages within the Mycobacterium tuberculosis complex, known as M. africanum West African 1 and M. africanum West African 2. These lineages are restricted to West Africa, where they cause up to half of human pulmonary tuberculosis. In this review we discuss the definition of M. africanum, describe the prevalence and restricted geographical distribution of M. africanum West African 1 and 2, review the occurrence of M. africanum in animals, and summarize the phenotypic differences described thus far between M. africanum and M. tuberculosis sensu stricto. © 2010 de Jong et al.
Finney O.C.,MRC Laboratories |
Finney O.C.,London School of Hygiene and Tropical Medicine |
Riley E.M.,London School of Hygiene and Tropical Medicine |
Walther M.,MRC Laboratories
Trends in Immunology | Year: 2010
T cell-mediated inflammatory immune responses contribute to both the clearance and pathology of malaria infections; the host's ability to down-regulate inflammation once parasitemia is controlled is crucial to avoid immune-mediated pathology but remains poorly understood. Various regulatory populations of T lymphocytes can modulate inflammatory immune responses and there has been considerable recent interest in the potential for regulatory T cells to modify the outcome of both murine and human malaria infections. Here, we review these studies, focussing in particular on recent studies in humans, propose a model by which different regulatory T cell populations might contribute to the control of inflammation at different stages of infection and discuss the implications for the design of safe and effective malaria vaccines. © 2009 Elsevier Ltd. All rights reserved.
Dominguez-Salas P.,London School of Hygiene and Tropical Medicine |
Dominguez-Salas P.,MRC Laboratories |
Cox S.E.,London School of Hygiene and Tropical Medicine |
Prentice A.M.,London School of Hygiene and Tropical Medicine |
And 3 more authors.
Proceedings of the Nutrition Society | Year: 2012
Evidence is growing for the long-term effects of environmental factors during early-life on later disease susceptibility. It is believed that epigenetic mechanisms (changes in gene function not mediated by DNA sequence alteration), particularly DNA methylation, play a role in these processes. This paper reviews the current state of knowledge of the involvement of C 1 metabolism and methyl donors and cofactors in maternal diet-induced DNA methylation changes in utero as an epigenetic mechanism. Methyl groups for DNA methylation are mostly derived from the diet and supplied through C 1 metabolism by way of choline, betaine, methionine or folate, with involvement of riboflavin and vitamins B6 and B12 as cofactors. Mouse models have shown that epigenetic features, for example DNA methylation, can be altered by periconceptional nutritional interventions such as folate supplementation, thereby changing offspring phenotype. Evidence of early nutrient-induced epigenetic change in human subjects is scant, but it is known that during pregnancy C 1 metabolism has to cope with high fetal demands for folate and choline needed for neural tube closure and normal development. Retrospective studies investigating the effect of famine or season during pregnancy indicate that variation in early environmental exposure in utero leads to differences in DNA methylation of offspring. This may affect gene expression in the offspring. Further research is needed to examine the real impact of maternal nutrient availability on DNA methylation in the developing fetus. © 2011 The Authors.
Biering-Sorensen S.,Statens Serum Institute |
Aaby P.,Statens Serum Institute |
Napirna B.M.,Hospital Nacional Simao Mendes |
Roth A.,Statens Serum Institute |
And 4 more authors.
Pediatric Infectious Disease Journal | Year: 2012
A total of 105 low-birth-weight children presenting for first vaccination were randomized to receive bacillus Calmette-Guérin (BCG) immediately or later (current practice). The mortality rate ratio for BCG was 0.17 (95% CI = 0.02-1.35) within 3 days of enrollment, 0.28 (0.06-1.37) in the first month, and 0.27 (0.07-0.98) after 2 months of age. The mortality rate ratio was 0.41 (0.14-1.18) (P = 0.098) in infancy. Administration of BCG vaccine at first contact may contribute to lower mortality. Copyright © 2012 by Lippincott Williams & Wilkins.
Grossman S.R.,The Broad Institute of MIT and Harvard |
Grossman S.R.,Massachusetts Institute of Technology |
Grossman S.R.,Harvard University |
Andersen K.G.,The Broad Institute of MIT and Harvard |
And 30 more authors.
Cell | Year: 2013
Although several hundred regions of the human genome harbor signals of positive natural selection, few of the relevant adaptive traits and variants have been elucidated. Using full-genome sequence variation from the 1000 Genomes (1000G) Project and the composite of multiple signals (CMS) test, we investigated 412 candidate signals and leveraged functional annotation, protein structure modeling, epigenetics, and association studies to identify and extensively annotate candidate causal variants. The resulting catalog provides a tractable list for experimental follow-up; it includes 35 high-scoring nonsynonymous variants, 59 variants associated with expression levels of a nearby coding gene or lincRNA, and numerous variants associated with susceptibility to infectious disease and other phenotypes. We experimentally characterized one candidate nonsynonymous variant in Toll-like receptor 5 (TLR5) and show that it leads to altered NF-κB signaling in response to bacterial flagellin. PaperFlick: © 2013 Elsevier Inc.
Hill P.C.,University of Otago |
Ota M.O.C.,MRC Laboratories
The Lancet Infectious Diseases | Year: 2010
The study of the contacts of patients with tuberculosis has a long history. Where tuberculosis is endemic, regular recruitment of tuberculosis cases and their household contacts can be done for research and strategic intervention. This recruitment provides a platform whereby host, pathogen, and environmental factors related to tuberculosis can be investigated and new interventions can be assessed. We describe the types of study possible within a tuberculosis case-contact study platform and its essential components, including recruitment and follow-up of the patients with tuberculosis, their household contacts and community controls, assessments and sampling, and data management and processing. Sample handling and storage, local engagement, ethical challenges, and the strengths and weaknesses of study design are all important issues in case-contact research. A case-contact study platform is a powerful research tool to answer fundamental questions in tuberculosis and has relevance to the study of other major infectious diseases. © 2010 Elsevier Ltd.
Bah E.,MRC Laboratories
IARC scientific publications | Year: 2011
The national cancer registry of the Gambia was established in 1986 as part of the Gambia Hepatitis Intervention Study in collaboration with IARC, France; Medical Research Council (MRC) Laboratories of the UK; and the Government of the Gambia at MRC, Banjul. Registration of incident cancer cases is done by active and passive methods. For this study, the registry contributed data on survival for six cancer sites or types registered during 1993-1997. Follow-up has been carried out predominantly by active methods with median follow-up ranging between 1-6 months. The proportion of histologically verified diagnosis for various cancers ranged between 1-45%, and 54-82% of total registered cases were included for survival analysis. Complete follow-up at five years from the incidence date ranged between 81-98% for different cancers. The 5-year age-standardized relative survival for selected cancers were cervix (23%), non-Hodgkin lymphoma (22%), breast (10%), stomach (4%) and liver (3%). The 5-year relative survival by age group showed fluctuations with no definite pattern or trend emerging, and with no survivors in many age intervals.